A clinical trial sponsored by University Hospital, Basel, Switzerland for a research study of Sodium chloride 0.9%, Conestat alfa

Brief description of study

Iodinated contrast media have been causally linked to acute kidney injury known as
contrast-induced nephropathy (CIN), which is the consequence of CM-induced local renal
ischemia and direct toxic effects. Conestat alfa (recombinant human C1 esterase inhibitor)
has been shown to decrease renal ischemic damage in experimental models of renal ischemia.

The Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy
in High-risk Subjects (PROTECT) Study is a randomized, placebo-controlled, double-blind
single-center trial that will assess the effect of prophylactic administration of Conestat
alfa on the degree of acute kidney injury subjects undergoing elective coronary angiography.
Patient with an estimated glomerular filtration rate <=50 ml/min/1.73 m2 and at least one
additional risk factor for CIN will be enrolled and randomly assigned to 1) Conestat alfa at
50 U/kg given as intravenous injection immediately before and 4 hours after coronary
angiography or 2) placebo (sodium chloride). All patients will receive standard intravenous
hydration with isotonic saline. Surrogate markers of kidney injury will be assessed over a 48
hours time period. Patients will be followed for cardiovascular and renal events over 12
weeks.

Detailed Study Description

Iodinated contrast media (CM) are an essential component of contemporary imaging and
interventional studies. Although CM are generally well tolerated, they have been causally
linked to acute kidney injury known as contrast-induced nephropathy (CIN), the third leading
cause of acute kidney injury in hospitalized patients. Preexisting renal impairment, diabetes
mellitus, advanced age, congestive heart failure, or large volumes and repeated use of CM
have been identified as risk factors for CIN. CIN is the consequence of CM-induced local
renal ischemia in combination with direct toxic effects to renal tubular cells. Subsequent
inflammation may cause further tissue damage in the reperfusion period. Apart from
intravenous hydration preventive strategies for CIN are lacking.

The complement system consists of several circulating proteins that are implicated in the
first-line defence against pathogens and in the removal of dying cells. Following renal
ischemia activation of the lectin pathway of complement in particular has been associated
with local tissue damage in the kidney. Conestat alfa is a recombinant human C1 esterase
inhibitor, which inhibits activation of the complement system and is licensed in Europe and
USA for the treatment of a hereditary condition (hereditary angioedema). Conestat alfa
markedly reduced tissue damage in experimental models of renal ischemia and reperfusion
injury, but has not been investigated in human ischemia.

The Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy
in High-risk Subjects (PROTECT) Study is a randomized, placebo-controlled, double-blind
single-center trial that will assess the effect of prophylactic administration of Conestat
alfa on the degree of acute kidney injury subjects undergoing elective coronary angiography.
Patient with an estimated glomerular filtration rate <=50 ml/min/1.73 m2 and at least one
additional risk factor for CIN will be enrolled and randomly assigned to 1) Conestat alfa at
50 U/kg given as intravenous injection immediately before and 4 hours after coronary
angiography or 2) placebo (sodium chloride). All patients will receive standard intravenous
hydration with isotonic saline. Surrogate markers of kidney injury including serum creatinine
and cystatin C and urinary Neutrophil gelatinase-associated lipocalin and TIMP2 *
Insulin-like growth factor-binding protein 7 (IGFBP7) will be assessed over a 48 hours time
period. In addition, increases in troponin T, a marker of cardiac damage, will be assessed.
Patients will be followed for thromboembolic, anaphylactic and a composite endpoint of
cardiovascular and renal events over a 12 week period.